One-pot catalytic strategies for the efficient and enantioselective synthesis of L-Carnosine

The global market for L-Carnosine is experiencing consistent growth, driven by its expanding applications in nutrition, therapeutics, and cosmetics. L-Carnosine, a dipeptide composed of β-alanine and L-histidine, plays a pivotal role in reducing oxidative stress and supporting energy metabolism, with demonstrated therapeutic potential in conditions such as diabetes, Alzheimer’s disease, and Parkinson’s disease.[1] In pursuit of a more sustainable and efficient synthetic route to L-Carnosine with high yield and enantiopurity, we developed a one-pot protocol strategy (Figure 1) starting from ethyl methyl (Z)-2-(2-cyanoacetamido)-3-(1H-imidazol-4-yl)acrylate, identified as a Privileged Precursor (PP) of L-Carnosine. Asymmetric reduction of the C=C bond in the PP using [RhCOD(R,R)-Ephos]+TfO- was followed by hydrogenation of the cyano group with a Rh/C heterogeneous catalyst under basic conditions.[2,3] This sequence was performed in the same reactor avoiding any purification step and affording directly L-Carnosine in an overall yield of 68% and up to 73% enantiomeric excess, as confirmed by HPLC-MS analysis. While the protocol significantly streamlines the synthesis and purification processes, further optimization is ongoing to support its potential industrial application.[4] [OC-10A]